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spk06: Welcome to Natera's 2021 fourth quarter and full year financial results conference call. At this time, all participants are on a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at the time, please press star followed by one on your touchtone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this conference call is being recorded today, February 24th, 2022. I would now like to turn the conference call over to Michael Brophy, Chief Financial Officer. Please go ahead.
spk03: Thanks, operator. Good afternoon. Thank you for joining our conference call to discuss the results of our fourth quarter of 2021. On the line is Steve Chapman, our CEO, and Solomon Moskovich, General Manager of Oncology. Today's conference call is being broadcast live via webcast. We will be referring to a slide presentation that has been posted to investor.natera.com. A replay of the call will also be available at investor.natera.com. During the course of this conference call, we will make forward-looking statements regarding future events and our anticipated future performance, such as our operational and financial outlook and projections, our assumptions for that outlook, market size, partnerships, clinical studies, opportunities, and strategies, and expectations for various current and future products, including product capabilities, expected release dates, reimbursement coverage, and related effects on our financial and operating results. We caution you that such statements reflect our best judgment based on factors currently known to us and that actual events or results could differ materially. Please refer to the documents we found from time to time with the SEC including our most recent Form 10-K or 10-Q and the Form 8-K filed with today's press release. Those documents identify important risks and other factors that may cause our actual results to differ materially from those contained in or suggested by the forward-looking statements. Forward-looking statements made during the call are being made as of today. If this call is replayed or reviewed after today, the information presented during the call may not contain current or accurate information. Materials claim any obligation to update or revise any forward-looking statements. We will provide guidance on today's call, but will not provide any further guidance or updates on our performance during the quarter unless we do so in a public forum. We will quote a number of numeric or growth changes as we discuss our financial performance. And unless otherwise noted, each such reference represents a year-on-year comparison. And now, I'd like to turn the call over to Steve. Steve?
spk13: Great. Thanks, Mike. Good afternoon, everyone, and thank you for joining us. We've got a packed session full of announcements, so let's get into the recent highlights. 2021 was a breakout year for Natera. Volumes were up 53% year on year, which is higher than we pre-announced in January by more than 5,000 units. Despite all the disruption of the world from the Omicron variant, volumes were still very strong. We posted another record with 439,000 tests processed. In addition, this was also one of the largest sequential growth quarters we've ever seen on a net unit basis. Revenues were $625.5 million for the full year, above the top end of our November guidance, and more than $100 million higher than the midpoint of our original revenue guide given in February of 2021. Looking at the quarter, once again, Q4 was a very strong revenue quarter as we came in at roughly $173 million. Mike and I will spend more time on the drivers behind these numbers and the remaining financial results shortly. In addition to the excellent volume and revenue performance, we recently set a new standard for clinical data in the field of cell-free DNA with presentations and publications that can have a very meaningful impact on patient care. First is the recent presentation at the ASCO GI Conference from the prospective multi-site CIRCULATE trial, which showed that Signatera is predictive of treatment benefit in colorectal cancer. We also showed that Signatera has exceptional sensitivity at the post-surgical time point. This was the largest prospective data set ever presented using MRD testing in CRC, and the first to show MRD testing is predictive of treatment benefit in CRC. Second is the publication of the prospective multi-site smart trial in the Gray Journal, which is a leading journal in obstetrics and gynecology. With the SMART trial getting into publication in a top journal and with over 18,000 patients in the study, this now allows 22Q screening to be formally considered for ACOG guideline inclusion. There's a generally accepted set of criteria required for a disorder to be included in the prenatal testing guidelines, and we believe the study results achieved all of the performance metrics required to meet this objective. Finally, in organ health, we were able to release very strong, large-scale prospective data in each heart, lung, and kidney transplantation that we think can have a very positive impact when published. For example, in kidney, the trifecta study represents the largest prospective fully biopsy match study conducted to date, with nearly three times the number of biopsy match rejections as the DART study, which is one of the larger historical data sets in the space. We are very pleased that Prospera's performance in the study was exceptional, and we'll spend more time on all of these results later in the call. Finally, we are pleased to be guiding full-year 2022 total revenues at $770 to $790 million, which implies roughly 31% pro forma revenue growth over 2021 at the midpoint. The guide reflects our usual cautious approach, but there's upside opportunity as we see ourselves entering 2022 strongly positioned for continued growth across our portfolio. Okay, let's get into some of the business trends. The next slide is just an annual view of our volume growth over time. We have a long track record of execution, but you can see that something different happened in 2021 where we are benefiting from two fundamental trends in healthcare. First, the use of cell-free DNA in organ health and oncology is just getting started, and we are a leader in both fields. The volume from cancer products and organ health products are starting to make a significant impact on our growth. Second is the increased pace of NIPT adoption in the U.S., post ACOG guidelines, which drives not only NIPT volumes, but also allows us to offer physicians other tests like carrier screening and 22-2. I think our 2021 performance shows we are well positioned to leverage these trends, and we think these are multi-year drivers that we can continue to benefit from in the future. Diving into a quarterly view on the next slide shows that the business trends remain very strong in Q4 with total revenue growth outpacing volume growth. In addition, Quarterly sequential volume growth was strong at roughly 8%. This was one of the best sequential growth quarters we've ever had in spite of the fact that third quarter in 2021 was unusually strong for us because a large NIPT player exited the space in June and Q4 has fewer sessioning days due to the holidays. The underlying ASP performance was strong although we also had roughly $7 million in cash receipts from prior period true-ups and reserve benefits in Q3, which mutes the reported sequential pricing trends in Q4. $173 million in revenue was also well above expectations, and all the growth trends continue to look quite strong so far in Q1. On the next slide, I'm excited to share a new snapshot of the volume trajectory in our newer products. which, as you can see, have been growing rapidly. This is what I mean when I say cell-free DNA is just getting started in oncology and transplantation. The left chart is our volume progression in Signatera and Altera in oncology, and the right chart is Prospera and Renocyte in organ health. In oncology, the vast majority of these volumes are Signatera units ordered by physicians for clinical use, but this also includes very strong pharma performance. Based on our current run rate and publicly available data, We believe that we're very close to being the overall market leader by volume in the field of liquid biopsy, even when including both therapy selection and MRD testing categories. We think this performance is superior to any other MRD test on the market today. In addition, this rapid growth shows how big the MRD opportunity can be. We've been able to drive this level of early adoption, focusing primarily on colorectal cancer, which we think is still an underpenetrated market. Despite our historical focus on CRC, which represents less than 10% of the overall MRD opportunity, we are starting to see more volume come in for immunotherapy response monitoring in addition to MRD testing in other solid tumors beyond CRC. Some doctors start using signatera in colorectal cancer and then expand to use it as a multi-cancer tool. This is an advantage of our patient-specific tumor-informed assays. The same product can be applied to a broad range of cancer types without designing a new fixed panel for each tumor type. This growth is also impressive because 2021 was a building year for us with regards to our commercial and operational teams. We've now built a full commercial team that still has a lot of leverage left for growth. Paired with that, our robust lab operations now allow us to scale as we built out the infrastructure to optimize turnaround times and manage recurrent orders, both of which take time to master. We're in a great position to grow the market, but I think what's most impressive is our data leadership. We've got paradigm-shifting predictive data now in both colorectal and bladder cancers. We have over 100 additional studies underway, and it's possible we could publish more than 20 peer-reviewed papers in 2022 alone. In addition, in 2022, we will be receiving repeat testing volume from patients that started on Signatera in 2021, which is when the vast majority of our current patients initiated testing, driving continued growth for us. Overall, we believe we're in a very strong position to expand our leadership here and in the liquid biopsy field. In organ health, the majority of our volume in the slide is coming from Prospera orders, but it does also include a meaningful contribution from Renocyte. In 2022, we expect added momentum from the publication of the trifecta study in kidney, and we expect meaningful volume from the contribution of our recent launches in heart and lung, resulting from the publication of leading studies in those organs. It's worth noting that the commercial and operational infrastructure needed to support years of growth is largely built now, so we have an opportunity to get significant leverage out of our current team as centers adopt donor-derived cell-free DNA testing. You can see from this volume trajectory why we think we are positioned to be a top player in this space for years to come. For now, we will plan on providing the snapshot once annually on the Q4 call in order to preserve competitive positioning, but I think the 2021 volumes show that these are not going to be niche products, and we are on the path to achieving scale in these new areas. Now, let's move to the second major trend on the next slide. After gaining a full ACOG endorsement in 2020 for NIPT, adoption grew significantly in 2021. Even as the overall market for NIPT grew, based on our estimates, Panorama actually increased market share. As you can see on the right side of the chart, there is still a long way to go to get anywhere near full adoption. We've estimated that the NIPT market can reach 80 to 90 percent adoption in the coming years. In addition to growing adoption in the community setting, we are seeing growth from large group practices and health systems. For example, we recently just closed a system of over 10 hospitals that's now rolling out NIPT to its patients for the first time. We think that our competitive edge in winning these deals is our significant body of peer reviewed political evidence, our highly differentiated product, and our strong suite of user experience tools. For example, we're now fully integrated into leading EMR systems, making it easier for systems to adopt Panorama broadly. Additionally, Although it's the only state-sponsored prenatal screening program we are aware of in the United States, we think the state of California is likely to expand their existing prenatal screening program from high-risk only, in which Natera is already actively participating, to now include average-risk NIPT. We've been selected to participate in this program and are currently in discussions with the state. If we do choose to move forward, we would likely offer a lower-priced offering that screens for a narrower set of conditions, but we think that volume would increase as access is opened up by this program. We've already submitted for a unique PLA code for the more limited offering. In addition, we expect to offer other tests in our portfolio, like carrier screening, alongside the program as we enter new OBGYN offices. There are also a lot of key points in the program that are still under discussion, But we've gone ahead and built this into our forecast, taking a conservative approach to the impact of the change. Across all channels, OBGYN, MFM, hospital systems, et cetera, we think Natera remains very well positioned to extend its leadership position. The other opportunity that we see potentially compounding the value of increasing NIPT adoption is our ability to service the physician for additional tests that are routinely offered early in pregnancy. We think there are substantial growth opportunities here as our commercial team meets with more and more physicians to also expand our client base for other tests like genetic carrier screening that ACOG recommends to be offered to all pregnant women, regardless of ethnicity or age. Historically, Natera's carrier screening orders have scaled up together with our NIPT volume, and we think that trend will continue. Furthermore, we believe screening for the 22Q may soon be recommended as part of routine practice, which may further expand the value we can offer to our patients in ordering physicians. More on that topic on the next slide. As many of you saw in our press release, the landmark SMART 22Q microdeletion study was recently published in the Gray Journal, which is a premier journal among OBGYNs in the United States. SMART is by far the largest prospective study that confirmed genetic outcomes on all pregnancies in the study. The results were excellent. The incidence of 22q in the study was 1 in 1,524, which confirms 22q is one of the most common prenatal genetic disorders in the general population. And unlike trisomy 21, the incidence of the disorder is not impacted by maternal age. By comparison, cystic fibrosis, which is screened routinely, has an incidence of approximately 1 in 3,500 in the general population, And trisomy 18 and 13 have an incidence of 1 in 3,000 and 1 in 5,000, respectively. Panorama test results were accurate greater than 99.9% of the time, meaning that 99.9% of the time, the panorama result, whether high-risk or low-risk, was confirmed to be correct. For high-risk results only, we had a positive predicted value, or PPV, of 53%. meaning that more than one in two pregnancies screening high risk with panorama were confirmed to be effective using a confirmatory diagnostic test. This is really strong, especially compared to traditional prenatal tests like the quad screen offered routinely to all pregnant women in the United States for the past 40 years that have a PPV of only three and a half percent or one in 29. So the question remaining is, will this be recommended by ACOG for routine screening? Well, We don't control the outcome, but screen tests that offer the most clinical utility meet a few criteria. They screen for a serious disorder with high accuracy and high PPV. They catch many cases that are not otherwise captured by the existing standard of care, and early detection provides an opportunity to intervene and improve outcomes. In the case of 22Q, that means treatment with calcium at birth in order to mitigate potential seizures that can result in cognitive impairment. We think our 22Q microdeletion screen clearly meets all of these criteria. It's common, it's severe, it can be screened for with high accuracy, and there's an appropriate intervention. This sets up very nicely for a guideline change, but we will have to see where things end up. Okay, now let's spend a bit more time on the organ health opportunity. You saw the excellent traction we've been getting in Prospera on the earlier slide, and we see a lot of room for future growth. When we presented this slide in 2020, we estimated fewer than 5% of transplant recipients were getting cell-free DNA testing. While that has clearly grown, we think this chart shows PROSPERA can fill a significant unmet need in the coming years in what we believe is yet another large market opportunity. One driver we think can help increase adoption of cell-free DNA in this area is additional large prospective clinical trials that confirm the excellent performance of PROSPERA. While we're pleased with the data we generated thus far, we know that publishing the big prospective trials can really move the needle. Although our volume has been growing nicely, this is probably the biggest objection we face to the field. So just as we did in oncology and women's health, we've been investing heavily in data generation. Finally, after a ton of work by our team and our outside collaborators, in 2022, we expect a wave of prospective, strong, and meaningful data across kidney, heart, and lung transplantation, and we think this can make a significant impact for us. So first, a minute on the Trifecta study in kidney transplantation. This study was led by Dr. Phil Halloran, who's one of the premier researchers in the field. Trifecta had more than three times the number of biopsy match rejections than the DART study. Trifecta also enrolled patients from more than 20 U.S. and international sites. You can see the PROSPERA results from the initial readout were exceptional. The results were so strong that we believe it could eliminate the need for multimodality testing to rescue test performance. Multimodality testing using RNA and cell-free DNA is very expensive. We think it could cost roughly $6,000 per blood draw compared to PROSPERA, which is less than half of that price. So we look forward to publishing the trifecta study this spring, and we think it will be a really significant step forward for PROSPERA adoption. We also have two studies soon to be published in each of heart and lung transplantation. First in lung, we were pleased last fall to pre-release data from the largest prospective lung donor-derived cell-free DNA trial to date using a commercially available assay. The data was very strong and accepted for an oral presentation at ISHLG. We look forward to the publication of this paper in the near term. Finally, in heart, We previously announced the readout of our multi-site study that includes a prospective and retrospective arm. We showed an excellent overall AUC of 0.84 with greater than 250 prospective samples included in the study and greater than 100 retrospective samples for a total of greater than 350 overall. In fact, the AUC in the prospective arm was slightly higher than the retrospective arm. Again, This performance is very strong. It could eliminate the need to perform expensive multimodality tests that, in the context of heart transplantation, require cumbersome specimen processing, for example, spinning down the sample and shipping it on dry ice. Okay, now let me hand the call over to Solomon to provide an update on ecology. Solomon?
spk09: Thanks, Steve. We're now working across all three of these areas on the slide here. for an estimated total addressable market north of 50 billion. Given we just provided an update on the early cancer detection program earlier this year, the key focus of this business update will be on the MRD space and the Signatera opportunity. As many of you know, we've had several major wins recently, so I'm excited to elaborate. Let's start with the commercial and operational teams that we have built over the last 18 months or so. Steve touched on the competitive advantage we think this team is already delivering, and I think the signature volumes in 2021 proved that out. The commercial team is now similarly sized as the big teams from other liquid biopsy players. They've been in place with consistent sales territories for only a couple of quarters, so we think there's ample room for our team to get more efficient with initiating new clinics and supporting growth within existing accounts. We estimate the commercial team is only at roughly 10% capacity, in terms of the number of ordering patients and accounts that they can manage. Over the same time, we've also dramatically scaled our operations and launched flexible and intuitive user experience tools for seamless ordering of the test. No other company in the space has ever reached this level of scale with a personalized serial monitoring test. So we've solved a lot of new challenges to get to this point. On lab operations in Q4, we saw a median turnaround time of 19 days for a patient's initial test results and less than a week for subsequent tests. This means we're delivering test results within a clinically meaningful timeframe to inform adjuvant treatment decisions, especially since Signatera can be initiated at any time pre- or post-surgery, unlike other assays that are indicated only starting at 30 days post-surgery. Other laboratories that have ambitions to launch a tumor-informed MRD test will have to solve many of these same operational challenges, but with the added pressure of Signatera already being commercially available. Our suite of user experience tools are also making an impact, which of course leverage everything we've learned from operating in competitive environments for the last 10 years. The core of this offering are the online portals, EMR integrations, and a customer support infrastructure that is designed to facilitate serial monitoring and can be adjusted to fit the unique evolving needs of every patient. As Steve mentioned, we think the strongest components of our offering are the clinical performance of the test itself and the extensive validation data we've already produced and continue to produce across a broad range of cancer types. We expect our lead in data generation to only increase this year. We've now got more than 100 clinical studies in our pipeline, including projects with pharma partners and academic partners, and we expect a strong year of peer-reviewed publications, as Steve described. On the subject of clinical data, We were glad to host many of you for a special call about the data that was presented in January at ASCO GI. The interim readout from Circulate Japan included analysis from over 1,000 patients with 12 months of follow-up stratified by MRD status and, for the first time, also stratified by treatment status, which enabled the predictive claims that we can now make about Signatera in colorectal cancer. I want to just briefly review our results there and the next steps. So the central question for us in CRC has always been, will MRD positive patients benefit from adjuvant treatment, or are they just destined to recur regardless of treatment? This data clearly shows that Signatera positive patients do benefit from adjuvant chemotherapy. The green lines in these charts represent Signatera MRD positive patients that received chemotherapy, and the blue lines are the MRD positive patients that did not receive chemotherapy. you can see a clear separation of the lines, and the p-values were significant in all stages of disease, even when adjusting for other confounding factors such as age and lymph node status. The hazard ratios here are striking. For example, in the middle chart, we see stage three signatera positive patients are over eight times more likely to recur if they are observed instead of getting treated with adjuvant therapy. We know that a significant group of patients that are indicated for chemotherapy today do not actually get treated for a variety of reasons. Now, with the support of this interim data, we think it's going to be much more likely that MRD positive patients choose to pursue chemotherapy. Now, on the next slide, we address the other side of the coin. Would Signatera MRD negative patients benefit from chemotherapy, or can they safely avoid chemo while being serially monitored? You can see from the chart that there is no separation between the lines. which means the Signatera MRD negative patients received no significant treatment benefit from adjuvant chemotherapy in this study. Among patients who tested MRD negative at four weeks post-surgery, the 12-month survival benefit of adjuvant chemotherapy was not statistically significant, and it would not be worth the toxicity of chemotherapy. We believe this data could have an immediate impact for thousands of CRC patients who are already on the borderline about chemotherapy. and we look forward to confirming these results in future readouts from the trial. In addition to the predictive findings that I just covered, the prognostic data on the assay was also very strong, as we've shown before. Based on the single time point post-surgery, disease-free survival at 12 months was 95% for the signatera negative patients and 55% for the signatera positive patients, yielding a hazard ratio higher than 13%. Signatera sensitivity was 67% at the single time point, which is stronger than what was previously reported in our 2019 paper in JAMA Oncology. Overall, we think this test performance is really exceptional. The next slide is an updated snapshot of the addressable patient population in MRD that is built up from estimated tests per year. The short-term eligible population represents indications where we have already generated initial data and have line of sight to gaining Medicare reimbursement over the next two years, which we think together can support up to 4 million signatera tests per year in those indications. This now includes several GI indications outside of colorectal, including pancreatic, gastroesophageal, and anal cancers, where we've recently presented clinical data. Looking further out, we think prospective randomized trials may be required to unlock additional indications that, if successful, we believe could support Signatera volumes of up to 13 million tests per year. We're already working on generating that data, and we expect the first large prospective readouts over the next three to five years. Because Signatera is personalized and agnostic to tumor type, we have a great opportunity here to leverage the same product and the same commercial channel to drive adoption across all of these indications and to get significant leverage on our investments. Now, let's take a look at the coverage roadmap for the next few years. After receiving the initial MoldDx coverage decision in stage two and three CRC, and the subsequent umbrella policy was released, we have been able to rapidly follow up and win coverage in pan-cancer immunotherapy response monitoring and stage four CRC. We've now submitted additional indications to the MoldDx program, and we expect additional coverage decisions to come in in 2022 and 23. The key goal we have over that timeframe is to get into NCCN guidelines. We think the CRC data we presented from Circulate Japan, once it's peer-reviewed and published, merits consideration for guideline inclusion. The ASCO guideline update last December specifically referenced ctDNA as an emerging potential predictive factor, and it anticipated that forthcoming prospective data could merit inclusion in an upcoming future guideline. We have now generated that predictive data. And we'll further support that effort with additional readouts from Circulate, as well as data coming soon from Bespoke, our prospective registry trial in CRC. We'll take a similar approach with the other cancer types as well, generating additional evidence to support clinical utility across each of them. Although we feel good about our chances for NCCN guideline inclusion, it is ultimately outside of our control, so we do remain cautious in terms of the potential impact in our guide for this year. Now let me hand over the call to Mike to discuss the financials. Mike?
spk03: Great. Thanks, Solomon. I'll first recap how we finished 2021 and then move to the 2022 outlook. This slide is just the annual financial comparison. I think Steve and Solomon covered the volume and revenue trends well. Just to note a couple of factors Steve highlighted on our Q4 performance. $173 million of Q4 revenues represents roughly 9.4% sequential growth over Q3 2021 and test process through almost 8% sequentially over Q3. This is despite the fact that Q3 was an unusually strong quarter as Steve mentioned for us with one-time benefits both for volumes and revenues. So progeny exited the market in June and on the revenue side, we had roughly $7 million in incremental reserve and prior period true ups in Q3 versus Q4. In Q4, we only had about half a million in net trip revenue benefits, which is a little unusual for us in that we generally had something like 1.5 million to 2 million those quarters, but that's just part of the typical lumpiness that we've seen in the past. That lumpiness also creates some volatility in the quarterly gross margin, which is a little lower at 45.6% in the quarter. Another key driver of gross margins is, paradoxically, the success we are having with signature volumes. The P&L for Signatera is really immature right now, and I think it's poised to improve as we get further into the launch. A patient's first Signatera test is expensive for COGS since we run that upfront exome as a one-time event. We expect significant improvements in first-time point COGS in the next 18 months or so as we scale up. Subsequent volumes, of course, are much less expensive to run since we are just delivering the plasma test. So as an increasing percentage of our volumes come from repeat testing, the COGS per test on average should drift downward. The same logic applies for ASPs. We benefit from ADLT pricing and recurrence monitoring, and also we are in flight to receive reimbursement on a broader range of tumor types, as Solomon described. Given the strong organic adoption we have seen across tumor types, the relatively streamlined path to CMS reimbursement and the line of sight we have for potential guideline inclusion in colorectal cancer, which would drive commercial coverage in CRC. We think the best strategy to take advantage of our lead with Cigutera is to drive volume in multiple different cancers, even if this puts some modest pressure on gross margins in the immediate term. In contrast, underlying ASPs for Panorama, Horizon, and Prospera were strong in the quarter. We made some meaningful sequential gains in the Panorama ASP over Q3, as one of the larger plans suspended their prior authorization requirements for average risk in IPT. I think we still have significant room to improve on Panorama ASPs, given a large fraction of our NIPT volume is not yet reimbursed to that. The OpEx lines represent the scale-up of our commercial channels in transplant and especially oncology, as Stephen Solomon covered. In R&D, we have a couple of large projects focused on the next version of each of our core products. We are very excited about those and we'll be able to spend more time on these innovations on future calls. We also are developing products that can be used in conjunction with Signaterra, similar to the way that Altera is being used today. When thinking about R&D, it's worth a reminder that essentially all of our volume and revenue comes from products we have developed internally. Whether it's the development of the new algorithm used in the Smart Trial, or inventing Signatera, or launching innovations that dramatically reduce the cost of goods sold per unit, we've had a very high win rate with the investments we've made in our R&D effort. We expect that productivity to continue, particularly as we focus more on the next version of already successful products and inherently take less technical risk as a result. Another huge benefit from this internal development pipeline is that we haven't needed to pay a premium to acquire other companies. So we think this approach is also the most capital efficient path to future growth. R&D in 2022 also incorporates a major step up in clinical trial investment for Prospera and Signatera. For reflinks, clinical trial spend was roughly $20 million in 2020, and we expect it to be roughly $80 million in 2022. A large chunk of that increase is coming from the large randomized controlled trials going on right now. Once completed, they won't have to be run again. Given this increase, we've been selective with the trial-level fund. They must prove out clinical utility in a way that we think will drive broader adoption and or change practice guidelines. I don't think clinical trial spend needs to increase meaningfully beyond our expected 2022 levels to achieve our goals in the indication Solomon presented. Beyond that, we would pursue larger trials on a case-by-case basis and only on the back a very strong performance. The last major source of investment is capital expenditures required to scale the lab for all of this new volume. For context, we had about $19 million in CapEx in 2020, and we expect about $60 million in 2022. We'll get into this in the guide, but CapEx is also not something that needs to remain elevated, but we expect to transition to maintenance levels in the future. Just a note on the balance sheet, we exited the year with about $915 million in cash and equivalents, and we think this amount of capital will allow us to pursue all of the objectives we've outlined today. Okay, so that is a good segue to the 2022 guide on the next page. Overall, we think this is a bullish guide that implies significant revenue and volume growth while holding gross margins and cash flow stable versus last year as we continue to make the investments we've described today. We're guiding revenues of $770 million to $790 million. Proforma for the one-time Kynogen revenue recognition of $28.3 million in 2021. This represents 31% growth on top of the very successful year we just produced. Steve mentioned we took a note of caution with this guide. While case counts are thankfully down, we built in some conservatism in the volume forecast to account for Omicron and future COVID-19 spikes. While we haven't seen anything that would significantly disrupt our business, We want to err on the side of caution as each spike represents its own challenges. We do expect the new products volume to continue to grow, and that's based on the trends we've seen so far this year. On ASPs, on balance, we expect Signatera ASPs to improve this year, driven by expanded reimbursement and a higher mix of recurrence monitoring tests. This improvement is going to be held back a bit by the volume we're driving in tumor types that are not yet reimbursed, but we do expect net improvement in ASP this year. We've taken a cautious approach with the potential guideline inclusion and broader reimbursement for colorectal cancer. Solomon had that on his coverage roadmap and described this as a goal for 2022 and 23, so we are keeping that potential benefit out of the financial guide for this year right now since we don't fully control the timing. We expect stable ASPs in Prospera and Horizon, which is modestly more bullish than where we've been in the past. As a reminder, we normally bake in some ASP erosion into these products, but the underlying trends look much stronger than they have in the past several years. On prenatal testing, we think the trends for Panorama look strong, as I mentioned, and expect continued linear improvement and reimbursement. Steve mentioned the California Screening Program, which is a bit of a wild card since we haven't formally signed on to proceed. The guide incorporates what we expect right now, which is that we offer a narrower test at a lower price build on a test-specific PLA code. Practically speaking, the counter to this should be significant volume growth for anti-polluting volume and complementary products. In the guide, however, we've been very cautious with this part of the forecast. There are a lot of details we worked out, and we may not participate at all. So the contribution of the guide is an increase in volume from this narrower panel at a lower gross margin, with room left for upside on the other women's health products. The gross margin guide also reflects the expectation that we drive a lot of first-time Sidney Terra patients, as we talked about. Our gross margin in 21 pro forma for the Kyogen bump was about 46.7%, so this gross margin guide holds margin stable as we get through this launch phase with Signatera. Steve touched on the path to 22Q guidelines today, and while we feel very good about that process, the guide does not incorporate any meaningful change to 22Q reimbursement, given that it's not fully within our control. The drivers for R&D and SG&A are consistent with the Q4 trends I described. We've built a strong commercial team that we think can now get significant operating leverage from this point, coupled with a step-up in clinical trial spend in 2022. So the net of all that, expanding revenues, improving ASDs, scaling operations, is that we expect the 2022 cash burn to be roughly similar to last year. We think the commercial team build-out is reflected in this guide and to remain relatively stable in future years, even as the volumes continue to grow in these large markets we're pursuing. So even as we continue to make investments in R&D and lab capacity, we expect cash burn to start to go down meaningfully in 23 and 2024 based on the markets and products we are pursuing today. It's worth remembering that we've gotten scale like this before. In 2019, we said the number one goal of the company was to get the women's health offerings to cash flow break-evens. We did that by driving growth through ever greater efficiency from our sales teams, delivering excellent data, and securing broader reimbursement. Transplant and oncology offer a few new advantages. Many of the markets are much larger, most patients receive repeat testing, and we think the path to broad reimbursement is shorter, but fundamentally we are pursuing the same strategies that have worked for us in the past. So it's an exciting time for Natera, and we are very pleased to have been able to share these results with you. Now I'd like to turn it over to Q&A. Operator?
spk06: And thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by. We compile the Q&A roster. And our first question comes from Tia Savant from Morgan Stanley.
spk01: Your line is now open. Hey guys, good evening and thanks for the time here and congrats on a strong finish to the year and a healthy outlook. Maybe just to kick off on the guide, one for you, Mike. Can you share some color and what's included in terms of Signatera and Prospera contributions relative to reproductive health, at least directionally? And on a related note, given how far ahead of at least our model you were in terms of both Signatura and Prospera volumes, can you give us a sense of what fraction of that volume you're reimbursed on at the moment?
spk03: Yeah, sure. Thanks for the question. Yeah, so, you know, obviously as these businesses ramp, they're going to contribute an ever-larger proportion of of the volumes and the revenue as we go forward. I mean, I think that's the way that we've guided it. Having said that, I mean, there's a lot of pretty exciting dynamics happening in the NIPT space that may end up, you know, having women's health business grow quite rapidly, but obviously we've been more cautious with that part of the guide. So directionally, it's going to be an increasing portion of the revenue for 2022, and I think that's kind of implied by the, you know, by the ramp that you've seen here in 21. You know, the proportion of Cigna Terra that's reimbursed today is a minority of the volume just because of where we are on our reimbursement timeline. So, we've got volumes coming from, you know, multiple different cancer types, majority of which is colorectal cancer, but a significant minority is coming from other cancer types They're not yet reimbursed, although we're in flight on a number of, you know, additional, you know, reimbursement from OBEX on a number of additional tumor types. And then within colorectal cancer, of course, we're just reimbursed from Medicare, and Stephen Solomon laid the pathway out where we think we can potentially broaden that via guideline inclusion. So right now it's a minority that's getting reimbursed, and that's what's, you know, that's obviously reflected in the guide, although I did get some commentary in there presuming that we do make some progress in terms of the overall signature ASP this year.
spk01: Got it. Super helpful. And one quick follow-up for Solomon here, if I can. Solomon, on the MRD front, some of your peers here are starting to talk about more than 16 markers for their version of a tumor-informed panel for MRD. I was just curious as to your latest thoughts on what you think, you know, where diminishing returns to sensitivity begin to kick in, in terms of the number of variants. And then on the screening side, any early color from the FDA in accepting your RHS cohort in lieu of a prospective trial for colorectal screening?
spk13: Yeah, this is Steve. I'll take that, and then, Solomon, you can jump in. So, First of all, I think it's important to say on additional variants that we're already running broad variant panels in the RUO lab, and we have been for quite a while. If you remember with Panorama, we multiplex 13,000 probes in a single reaction. For us to develop an assay with 100 variants or 200 variants, it's really easy to do. We do that all the time. I think We chose 16 because we thought, you know, that was the right optimization for performance. And I think largely, you know, that's turned out to be true. So, you know, obviously we have capabilities to run broader panels, but we're really pleased with the performance that we're seeing today. I mean, look at our volumes in MRD testing. We think we're now getting very, very close to being the market leader overall in the entire field of liquid biopsy. you know, not just including MRD testing, you know, based on the tests that we have on the market today. So, you know, of course, we're always looking at opportunities to improve. There's multiple different things that we're doing right now, investing in the future of Signaterra. Additional variants is something that we can do easily if we chose to launch that, you know, in the CLIA setting. I think on early cancer detection, you know, we're not giving any additional updates today. I think our plan is to generate some data and hopefully have that, you know, toward the end of 2022, early 2023, that we can share publicly. We do plan on meeting with the FDA to discuss the R-Health study. You know, and as a reminder, you know, the R-Health study is not just a biobank of randomly collected samples. I mean, this was an IRB-approved early cancer detection study. very similar to, you know, many of the other studies that are being run today where samples are collected and then they're banked and then they're run at a singular time. So, you know, these are all prospectively collected samples under an IRB for the purposes of validating early cancer detection. The only difference is that we've been swapped in as the biomarker of choice, you know, versus I think others where the biomarker was, you know, defined initially and So I think we're in a good position. We're going to get some feedback, but you should plan on getting some data sort of toward the end of the year or the beginning of next year.
spk01: Got it. Very helpful. Thanks for the call, guys.
spk06: And thank you. And our next question comes from Pruneet Suda from SBB Learing. Your line is now open.
spk07: Hi, guys. Thanks for taking my questions. So the first one is on NIPT and another one on signature. So maybe just for the California screening program, I mean, could you maybe size that opportunity for us and what's the timing of that? And could you elaborate, you know, is that something exclusive to you or should we assume that you're going to maintain your sort of market share in that, you know, large opportunity?
spk13: Yeah, so as far as market share goes and things like that, I mean, we know that we've been selected. I believe there are other labs that are also being considered, although we don't know the exact details. It doesn't mean that we're definitively participating, but if we do, we think it's going to be a lower-priced assay where we'll offer less content. You know, we've applied for an individual PLA code there. We think we'll get to sell additional content alongside the program. So, you know, I think we're in a good position, but there's a lot of details, you know, that still need to be worked out there, you know, before we can really give a lot of the specifics. I don't know. Mike, do you have any other comments there? No, I think that covers it.
spk07: Yeah. Okay. And then on the Signatura and Altera volumes, I appreciate you providing the details here. It was clearly a significant pickup in the fourth quarter. And it's clear that you're emphasizing volume growth and indication expansion while ASP is expected to grow more longer term. you know, I think the biggest question here from investors is just sort of the growth rate that you're seeing here in Signaterra and volume. Maybe just give us a sense of sort of, you know, how should we imagine that for 2022 within the context of your guide? And given the fact that what Solomon said is you're only 10% of your commercial footprint right now. So, A number of factors are going into it, so anything you can provide and sort of the growth rates that we should be assuming for Signatura. I know it's still somewhat early days for the product, but that would be super helpful. And then I have just a final quick one for Mike on gross margin. Just want to understand, you know, what's the longer-term gross margin objective? The gross margin is a bit softer versus, you know, our expectations for 2022. Thank you.
spk13: So maybe I'll comment briefly on this kind of signature trajectory, and then, Mike, you can talk about, you know, how we incorporated that into the guide. You know, so obviously, you know, we've given an annual volume here, but, you know, of course this means on a sequential, you know, quarter-on-quarter basis, you know, things are accelerating. And, you know, we feel like at this point, you know, we're doing exceptionally well from a volume standpoint, you know, significantly better than any MRD company out there. And, you know, things are going really well. I mean, you know, we sort of know what other companies are reporting out publicly with regards to, like, their entire company's book of liquid biopsy volume. And, you know, as we said, we think we're very, very close to being the entire market leader for the entire book of liquid biopsy. So things are on a good trajectory. Mike, do you want to talk about the guide?
spk03: Yeah, so I think Steve covered it in terms of the volume growth and the trajectory, kind of similar to the answer to Teja's question. I mean, we expect both these products, based on the trend that we've seen so far this year, to continue to contribute and continue to grow. So they're an increasing percentage of the implied volume guide presented here. Part of the reason why we wanted to share the numbers, the volumes with you, is on the topic of gross margins. I mean, because this is a relatively low gross margin test right now, but over time, clearly, you know, a high gross margin test, we feel like it's worth it to be driving this volume here despite the kind of immediate term pressure on gross margins. We've talked about it in the past. I mean, nothing about the past year has dissuaded me from that concept that this ought to be a 70% plus gross margin business overall over time. And I think we can we've shown a lot of ability to drive gross margin traction for those of us on the call that have been around for four or five years and recall gross margins in the low 30s range, and we've driven them to this level. The gross margin guide implies basically a stable gross margin despite kind of a new wave of Sydney Terra tests that are coming in ahead of reimbursement. So what that implies is that the other products are really delivering a lot of gross margin leverage. And that's exactly what we're seeing in Prospera, Panorama, and Horizon, for example. So a bit of a dynamic situation, but I think on balance it's a bullish thing, and we think this is the right thing to do to make the investment, just given the demand that we're seeing and the traction that we have toward getting reimbursement from Molex and additional cancer types. Got it.
spk06: Okay. Helpful, guys. Thank you. And thank you. And our next question comes from Tycho Peterson from J.P. Morgan. Your line is now open.
spk10: Hey, good afternoon. On multi-cancer MRD, you mentioned you've submitted some additional indications to MoldyX. Can you just clarify, you know, which those are? And I guess you're expecting five to be reimbursed next year, so have you submitted all five at this point? And then you also alluded to some, you know, adjacent products like Altera. Can you maybe just clarify what you're talking about there and if that could come this year?
spk13: Yeah. So, you know, the guidelines basically state that you have to have published data before you can submit a tech assessment. And so, you know, if you look at, you know, the areas where we publish data, I think we now have 15 peer-reviewed papers in Signaterra, and we think this year we can publish an additional 20 or more papers, and we have 100 different clinical trials that are ongoing right now in the field of oncology. So I think it's really kind of targeting in on where we publish data. Those would be the candidates for submitting to MOLD-DX. And we think this, I think not only is it great because we get the performance of our product out there to talk to physicians, but You know, we think we're leading the field, and we have a significant margin on the number of studies, the number of papers, you know, that are out there. So, you know, things like, you know, bladder, for example, you know, is one of the areas where, you know, I think it would make sense for us to submit it and so forth. You know, and you can kind of go through the list if you flip back the slide of what's been published. Then as far as additional content goes, I mean, You know, one of the strategies that has worked really well for us in Women's Health that we talked about on this call is offering additional content, additional products, you know, at the same call point. And so Women's Health, you know, if we sell a panorama test, we can also sell horizon period screening, and we can also sell 22Q screening. So we think long-term in oncology will be the same way, where there will be a portfolio of products. You know, and so things like Altera, for example, therapy selection, something that we already have on the market today. I think liquid biopsy therapy selection is something that probably makes sense. And so, you know, as we talk about our R&D budget and, you know, the spending that we're doing there, you know, a lot of that is going towards making sure that we have a rounded portfolio long term and that we continue to invest in a very significant way into enhancements to Signatera.
spk10: Okay, that's helpful. And then on Panorama, can you just update us on your latest thinking around micro deletions? Could we get something this year?
spk13: Yeah, so I think we're, you know, at this point, we're sort of in a holding pattern. You know, we're waiting for the guideline committee to meet, and then we're going to see what the results are. I think, you know, it's definitely possible we could get something this year. I think the smart, the big news, you know, that's happened this year is is that the SMART study was published in the Gray Journal and the results were excellent. So, you know, all the other earnings calls, when we talked about this, we didn't have the results published. And so now I think we're at a point where the guideline committee can meet and they can assess, you know, whether they want to incorporate this into guidelines. So, you know, if you go back to the prepared, you know, we sort of ticked off all the different reasons why you know, we think this might, you know, meet the criteria. But, you know, ultimately, it's sort of out of our hands. But it, you know, certainly meets the criteria. And definitely, without a doubt, the publication that was the study that was done, you know, was very significant. And the fact that it's now published, you know, makes it eligible for coverage.
spk10: Great. And then just lastly, I know you don't want to talk about screening much at this point, but can you just clarify with the data set you have, will you be doing other cancers in parallel with that data set, or should we just think about data later this year around colorectal?
spk13: Yeah, I think the initial readout is going to be colorectal, you know, but I think longer term, you know, it makes sense to have a multi-cancer offering. But the initial readout that we'll be doing and the initial, I think, launch will be in colorectal.
spk10: Okay.
spk06: Thanks. And thank you. And our next question comes from Catherine Schult from Baird. Your line is now open.
spk00: Hey, guys. Thanks for the questions. I guess first, maybe on the ASP assumptions for NIPT and the guide, can you just talk about where you are in terms of getting state Medicaid plans to cover average risk and what kind of progress you expect on that front in 22?
spk13: Yeah, so, you know, that's been an area of continued improvement. I think, you know, there's still some commercial plans that we're still working on, you know, but there's a long tail of plans, including state Medicaid plans, you know, that are still kind of in the process of kind of putting coverage in place. And we think that, you know, has improved on an annual basis and is going to continue to improve in the future. You know, so certainly we're expecting some improvement there. Mike, do you want to comment on kind of your thoughts on like NIPT ASP trajectory?
spk03: Yeah. I mean, I think what we've presumed in the guide and the model is just kind of modest and linear improvement in the NIPT ASP over the course of the year. And I think, as we've talked about before, I think that's something that is poised to continue over a couple of years. as we just win reimbursement coverage from this long fail. And it's not just coverage decisions. It's, for example, you know, getting, you know, prior authorization requirements removed, which helped us actually sequentially in the quarter on the NIPT AST, as I mentioned, in the proposed remarks. So there's a laundry list of activities to pursue there. And on balance, you know, things look, you know, quite positive for the NIPT AST trajectory.
spk00: Okay, got it. And then you had a big step up in the licensing and other revenue in the quarter. Were there any one-timers in there? Was it really, you know, are you a Signatera-driven?
spk03: Yeah, I think it was a mix. I mean, we have... You know, as we got to some milestones with our progress with Foundation Medicine, you know, that was a contribution. But then also we had a very strong, you know, continued progress with Cigna Terra Pharma as the guy who made sure we prepared the most.
spk00: All right, great. Thank you.
spk06: And thank you. And our next question comes from Max Masucci from Cowan & Company. Your line is now open.
spk11: Thanks for taking the questions. One on transplant, just curious what portion of the transplant volumes are coming from competitive wins versus, you know, Greenfield or new adopters, and if the mix of volumes coming from competitive wins versus non-competitive has shifted at all over the last 12 months.
spk13: Yeah, so, you know, I think we're doing really well in transplant. You know, as we've said for a long time, but now, you know, Glad we finally are able to really share the volumes with you guys. You know, we did, you know, in Oregon Health, you know, greater than 42,000 units last year. I think that's, you know, really exceptional. You know, we see a mix. You know, there's some competitive wins and there's some greenfield wins. We're now, like, working with a very, very significant portion of the top transplant centers. You know, we've kind of outlined and sort of picked through that before. But, you know, if you go through the top 10 and you go through the top 50, I mean, we're working in, you know, the premier centers, many of the top centers. So we're doing really well. I do think, you know, our competitors in the space have done a good job growing their business. And, you know, they've proven that, you know, there's a very significant growth trajectory here and a very significant business here. And so I think we're on that same growth trajectory now, and, you know, we're pleased with our performance, and we're continuing to see momentum. I think one of the things that's going to accelerate our ability for competitive wins are these three major peer-reviewed papers that we expect to come out in 2022. That's, you know, the trifecta study in kidney. That's the large multi-site study in heart. And that's the perspective, the large perspective trial lung that we described earlier in the presentation. So I think we're in a good position, but things have the potential to accelerate.
spk11: Great. Maybe one for Solomon. I'd be curious to hear about the work you're doing in multiple myeloma and any other blood-based cancers and Just curious if you're using bone marrow or blood up front to design the follow-up test for myeloma.
spk09: Yeah, thank you for the question. We're very excited about solving a pretty big clinical unmet need in monitoring for patients with multiple myeloma. Today, those patients, in order to get MRD testing done, need to get serial bone marrow biopsies, which are painful and expensive and really therefore underutilized. So a lot of patients just aren't getting enough monitoring or as much as they want and as much as physicians think would be useful. We're able to do, to run Signatera the same way we do in solid tumors. So running it off of a blood sample, getting cell-free DNA, and analyzing the personalized assay there. We design that personalized signature from an analysis of several different specimen types that we've done in research. We presented data at a conference last year showing really strong performance that exceeded what you'd get from flow cytometry using FFPE samples as input followed by custom design of the assay and analysis in the plasma. So we think this could really improve care for thousands of patients. and we're looking forward to talk more about that when it's ready for market.
spk11: Great.
spk06: Thanks for taking the questions. And thank you. And our next question comes from Mark Macero from BTIG. Your line is now open.
spk08: Hey, guys. Thanks so much for the disclosures on oncology and transplant. I guess on the oncology side, again, Is it safe to say that the vast majority of the split between Signaterra and Altera is on Signaterra itself? And then secondly, I think in the past you've talked about Signaterra all in ASPs at around $500 per time point. Is that right? And then thirdly, Altera, should we think of that as getting reimbursed similar to like a Foundation One?
spk13: Yeah, so let me make a couple comments, and then maybe, Mike, you can talk to Solomon about the ASPs a little bit. But, yeah, the vast majority of volume here is Signatera. I mean, we launched that before Altera, but also it's a much, much bigger opportunity. And then we're only really promoting Altera in a targeted way as well. I mean, generally, for patients that want to get IO monitoring that are getting Signatera set up, we'll then also, you know, add Altera because of the convenience factor. So, you know, yeah, vast, vast majority in Signatera, you know, vast majority in colorectal, although we are, you know, starting to see growth in IO monitoring. And then, as we said, Nicole, more, you know, more of the pan cancer volume coming in. I think on the ASP side, on Altera, I think, You know, there's FDA-approved versions, you know, which get the premier kind of ADLT pricing. And, you know, we don't expect to get that. But, you know, I think we'd be participating at the kind of more general CMS rate. But, Mike, do you want to talk kind of about ASPs in general for Cignatera or Altera?
spk03: Yeah, so Mark, that's roughly right in terms of the ASP range for Cigna Terra. And you can see that that's a far cry from the price we get when we actually get paid. So we have the ADLT rate at $3,500 and the adjunct time point ASPs in the 2000s. So what that means is just we're driving a bunch of volume that are not yet reimbursed for Medicare or their commercial lives. And those are volumes that we think we can get reimbursed on in the relative near term. So we're pretty excited about the ASP trajectory for Signatera, given the reimbursement wins we've got on the door. It does mean that, you know, at the moment, you know, the ASPs are just quite mature. And as we've said in prepared remarks, even net of volume growth, in Signatera. We think some of these factors will drive the net ASP higher in the year, and that includes a higher, you know, mix of sequence monitoring tests and just a broader trend beat of reimbursement, reimbursement indications for mobile apps.
spk08: Okay, great. And then it certainly seems like there could be a step function increase in MRD testing as a, you know, now that Signatera I.O., is reimbursed. Is that fair? I mean, you know, the 76,000 was certainly very impressive for 21, but it seems like you guys are just getting started. 22, in my opinion, could be a step function increase. Would you agree with that? And then second part, have you received pricing yet for Signaterra IO?
spk13: Yeah, so I think we certainly are expecting growth. I mean, the trajectory is excellent right now. And, you know, as we said, kind of accelerating growth. you know, throughout 21. I think that the MRD testing opportunity versus the monitoring opportunity is still going to drive, you know, a lot of the growth, although IO is a big opportunity and we're starting to see that accelerate. You know, I think just when you just look at the number of patients available and, you know, I think where physicians are you know, more comfortable now using the test, and it's in that CRC MRD and recurrence monitoring setting. Yeah, so I would expect, you know, the vast majority to be there, but IO is certainly making a contribution, you know, and that contribution is growing. Remind me of the second part of your question. I apologize.
spk08: Yeah, have you received a price for Signature IO yet? If so, what is it?
spk13: Yeah, yeah. So we're still in the kind of final stages of that. You know, it's just the standard individual discussion with the MUL-DX program. I think our expectation is that's going to be kind of roughly similar to the adjuvant colorectal pricing where, you know, there's a bundled price, you know, for kind of the initial testing that occurs. And so we think it will be like kind of roughly similar to what we saw in that adjuvant bundle.
spk08: Got it. Okay, if I can sneak one final one. It looks like, I believe you're getting paid something around $28.41 per test for Prospera kidney. Are you getting paid on any commercial lives at this time? And then I imagine that the vast majority of that bucket was Prospera kidney as opposed to renosite.
spk13: Yeah, so right now there's really not any commercial coverage in place. I think that's an opportunity, you know, but we're seeing, you know, we're seeing, you know, Medicare consistently reimbursed, but really nothing from the commercial plans. And, you know, I think that could change over time. I think that's an opportunity for upside. You know, probably about half of the patients roughly are sort of Medicare at this point. As we're getting, you know, volume from transplant centers and also from the community nephrologists, you know, there are a decent number of commercial lives there. The contribution from heart and lung, it's currently available on the market. We're actually seeing good utilization there, but we're kind of very, very early stages. So those aren't really incorporated here in a meaningful way. And then renoside, you know, is in here. It is a meaningful portion of this, but the vast majority is Prospera.
spk08: Terrific. Thanks so much.
spk06: And thank you. And our next question comes from Dan Leonard from Wells Fargo. Your line is now open.
spk12: Thanks for taking the question. Could you share your thinking on the topic of price sensitivity and NIPT and does the California contract signal more price sensitivity or is that an isolated, you know, incident?
spk13: Yeah. So I think the, you know, what, what, what, what, what we think is, you know, this situation with California, we're still kind of working through the details is there's going to be a lower price offering that's going to have very limited content. And, you know, I think we, we've applied for a specific PLA code, from the AMA, which will kind of signify and be priced specifically, you know, for that more limited content. So I think California is unique. They've had a state program for probably, I don't know, 20 plus years. And, you know, I think it's not something that's sort of really been kind of deployed broadly across the United States. You know, I think we're considering whether we participate or not at this point. You know, if we do participate, You know, we think there's definitely volume upside as we access additional offices that we're not currently in. You know, so it's something, you know, we have to kind of assess and kind of take it from there as details emerge and as things crystallize.
spk12: And Steve, what does narrower content mean? Is this just Trisomy 21 or does it include 18 and 13? What would a narrower panel look like?
spk13: Yeah, you know, I think the details need to kind of be fully fleshed out. But, you know, from what we understand, it would be probably 21, 13, and 18, for example, only.
spk12: Thank you.
spk06: Sure. And thank you. And our next question comes from Alex Nowak. Greg, from Greg Hallam Capital, your line is now open.
spk02: Hey, Greg, good afternoon, everyone. It looks like the FDA is looking to use the New York Times investigation of the prenatal test here as some fuel for a broader push to regulate lab-developed tests again. Can you just comment on your thoughts there, what FDA's oversight might mean for the business?
spk13: Yeah, so, you know, we actually really support any additional regulatory oversight. I mean, we're already very heavily regulated. today, but we've looked at sort of this kind of valid act that's out there. We strongly support that. I think the good news is that we are by far, without a doubt, the most thoroughly validated NIPT product on the market today. We have significantly more patients that have been studied in clinical trials, and the largest multi-site perspective real-world studies that have ever been done in this space. So, you know, if there is regulation, which we completely welcome, we're in an excellent position, and we're in probably the strongest position out of anybody.
spk02: Okay, got it. And then we've been hearing that the multi-tech assessment process has actually been taking a little bit longer than what some were initially expecting. There's a couple examples out there in the markets. So I think some of that could be COVID backlogs, but just what are you hearing and then specifically seeing with regards to your own tech assessment process for new Cigna Terra indications?
spk13: That hasn't been our experience so far, but yeah, maybe I'll make some comments and then you can go ahead. Our experience so far hasn't been that way, but that doesn't mean that there's not delays. I think so far we've After getting the initial colorectal coverage, you know, we then additionally submitted a tech assessment for phase four CRC oligometastatic. And we got that, you know, I think last fall. So that was kind of a follow-on under the kind of tech assessment process after the peer-reviewed paper came out last spring. And then, you know, obviously we got the IO coverage, which was sort of part of the pan-cancer LCD that came out. We submitted multiple different tech assessments at this point, and we're in active discussions. Solomon, do you want to comment further?
spk09: Sure. I think certainly a year, year and a half ago, we were seeing Medicare backed up because they were reviewing so many submissions for new COVID tests coming to market, but they're not really seeing that from what we've heard you know, so much in the last few months. And exactly what Steve said, we're not seeing anything out of the ordinary right now. That's great to hear. Appreciate the update. Thanks.
spk06: And thank you. And our next question comes from Kyle Mikeson from Canon Corriginuity. Your line is now open.
spk04: Great. Hey guys, thanks for taking the questions. So you've mentioned segmentary volume is shifting in favor of the current monitoring settings. That's an ASP tailwind. Um, I guess just quickly, um, is there a PD repeat testing that you're spending for 22 and 23? Is that mostly CRC or is that other tumor types? And just obviously there's implications on reimbursement ASP on like a cancer type by cancer type basis. So I'm just kind of curious what you're thinking there for like next year and going forward.
spk13: Yeah. So the, The vast majority of orders that we see where the doctors, you know, kind of requesting a protocol are in the field of CRC, you know, but we are starting to see in the additional tumor types as doctors become comfortable, you know, they start to move to kind of a repeat order model. So we think, you know, over time it's going to be both, but, you know, the vast majority of patients The volume and the repeat orders is in CRC.
spk04: Okay, and then just a quick one for Mike. I think you were talking about this in your prepared remarks, but COGS per test, and that increases or stays flat in 21. Can you just confirm if that's true and then how COGS per test could evolve going forward and why that would decrease as the new products receive reimbursement?
spk03: Yeah, the reason why the COGs per test are going to go down is because we're just really immature, in particular, on the significant terror COGs. So we touched on the prepared remarks. One of the big projects in the R&D lab is to get more efficient on that first time point exome, which we think we can do. It's really more a matter of scaling up more than anything else. The COGs for the other projects, for the monitoring tests for Signatera and for NIPT and Prospera really kind of all leverage a lot of the core technology that we've developed here over time. And, for example, on NIPT, we've got, we think, a clear pathway from the 160 range to, you know, the 125 range or so over time and potentially lower. So it's a similar trajectory across the other products. So that's the path to reducing cost of goods sold per test. And we've got a lot of track record of doing that going back seven years plus. Okay.
spk04: Makes sense. Thanks, guys.
spk06: And thank you. And I am showing no further questions. This concludes today's conference call. Thank you for participating. You may now disconnect.
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